Assembly for use in a drug delivery device

ABSTRACT

The present invention relates to an assembly for a drug delivery device comprising a dispensing container and a reservoir container for holding a fluid medicinal product, wherein the dispensing container and the reservoir container are connected to one another and are in fluid communication, and wherein the dispensing container is squeezable for dispensing a dose of the fluid medicinal product from the dispensing container, the dispensing container being refillable with the fluid medicinal product from the reservoir container.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 13/319,923, filed Apr. 17, 2012, which is a U.S. National PhaseApplication pursuant to 35 U.S.C. §371 of International Application No.PCT/EP2010/056970 filed May 20, 2010, which claims priority to EuropeanPatent Application No. 09006823.0 filed on May 20, 2009. The entiredisclosure contents of these applications are herewith incorporated byreference into the present application.

FIELD OF INVENTION

The present invention relates to an assembly for use in a drug deliverydevice.

BACKGROUND

Drug delivery devices are generally known for the administration of amedicinal product, for example insulin, but also for other medicinalproducts for self-administration by a patient. Therefore, the drugdelivery devices should be safe and comfortable in use and shoulddispense an exact dose of a medicinal product. Most of the drug deliverydevices are pen-type injectors which can dispense a pre-set dose of amedicinal product.

In some cases it is necessary for the patient to get an exact volume ofa certain medicinal product. In most commercially available drugdelivery devices there are many sources of error for dispensinginaccuracy. One is for example the dripping out of the needle afterinjection and therefore the need to keep the needle in the skin afterinjection.

SUMMARY

It is an object to the present invention to provide an assembly for usein a drug delivery device which helps to improve the accuracy of adispensed dose.

According to a first aspect of the present disclosure an assembly for adrug delivery device is provided, the assembly comprising a dispensingcontainer and a reservoir container for holding a fluid medicinalproduct, wherein the dispensing container and the reservoir containerare connected to one another and are in fluid communication, and whereinthe dispensing container is squeezable for dispensing a dose of a fluidmedicinal product from the dispensing container, the dispensingcontainer being refillable with the fluid medicinal product from thereservoir container.

In the assembly, the dispensing container has an inner volume that isequivalent to a dose, whereas the reservoir container is holding aplurality of doses. The dose which may be enclosed in the dispensingcontainer can be dispensed in a single dispensing process or in severalsubsequent dispensing processes.

The dispensing container can be squeezed. While the dispensing containeris squeezed the fluid medicinal product is dispensed.

The fluid medicinal product that may refill the dispensing container iscontained in the reservoir container. The reservoir container and thedispensing container can have a permanent connection. This connection isconstructed such that the dispensing container can be refilled withfluid medicinal product from the reservoir container.

Some parts of the assembly, like for example the dispensing container,the reservoir container or the connecting means are in direct contactwith the fluid medicinal product. These parts have an appropriatechemical resistance towards the fluid medicinal product that iscontained. These materials can comprise PVC, silicone rubber orfluoropolymer.

In a preferred embodiment a connecting means is connecting an inlet ofthe dispensing container with a first outlet which is located at thereservoir container.

The connecting means can for example be a tube. A tube allows a fluidcommunication between the reservoir container and the dispensingcontainer.

The connecting means can be flexible. In case that the connecting meansis flexible it can provide a durable connection even if the distancebetween the dispensing container and the reservoir container variesduring the dispensing process.

In another preferred embodiment, a first control member is located in aconnecting flow path between the dispensing container and the reservoircontainer.

The first control member may be a check valve. This check valve canregulate the flow of the fluid medicinal product.

This regulation may affect the amount of fluid medicinal product, thetime frame in which the fluid medicinal product can flow through theconnecting means and the direction in which the fluid medicinal productcan flow.

The control member may be located at the first outlet of the reservoircontainer or at the inlet of the dispensing container. Alternatively,the control member can be located somewhere between the first outlet ofthe reservoir container and the inlet of the dispensing container.

In one embodiment the first control member allows the fluid medicinalproduct to flow only from the first outlet which is located at thereservoir container in the direction of the inlet of the dispensingcontainer.

In this embodiment a check valve may find use, wherein the medicinalproduct can flow through an opening in the check valve. The fluidmedicinal product can only flow through the opening in a certaindirection after a certain pressure is applied to the check valve.

Due to the one-way behavior of the check valve a reflow of medicinalproduct from the dispensing container into the reservoir container canbe effectively avoided. This leads to an improved accuracy of the dosagedispensed from the dispensing container because the enclosed volume ofthe fluid medicinal product in the dispensing container is exactlydefined.

In another embodiment a second control member is located in a dispensingflow path of a second outlet which is located at the dispensingcontainer.

The dispensing flow path of the second outlet which is located at thedispensing container is directed towards the dispensing end of theassembly. A needle unit can be attached to this dispensing end.

The second control member may be a check valve which allows the fluidmedicinal product to flow only in the dispensing direction which meansfrom the dispensing container in the direction where the needle unitmight be attached to the assembly.

In another preferred embodiment the second control member is preventingin taking of air or fluid or tissue into the dispensing container viathe dispensing flow path.

In taking of air or of tissue through the second outlet would lead to adose inaccuracy for the next dose which is dispensed from the assembly.Only the fluid medicinal product from the reservoir container shouldrefill the dispensing container, therefore the second control membershould prevent that dispensed fluid or blood flows back into thedispensing container.

One advantage of having a second control member is that the same volumeof fluid medicinal product is enclosed inside the dispensing containerbefore a dispensing process is started and after the fluid medicinalproduct dispensed during this dispensing process is refilled from thereservoir container.

In one preferred embodiment the second control member allows the fluidmedicinal product to be dispensed through the second outlet which islocated at the dispensing container.

The second outlet can be located diametrically opposed to the inlet ofthe dispensing container. In particular, a pen-type injector can beformed through a linear alignment of the components of the assembly.

While dispensing the fluid medicinal product the second control memberopens the flow path in direction of a needle unit which might beattached. The injection takes place by means of the attached needleunit.

In another preferred embodiment the dispensing container comprises ahollow body.

The hollow body can for example be formed as a hollow sphere. The innervolume of this hollow body is equivalent to the maximum volume that canbe dispensed at a time.

The dispensing container can also be pear-shaped.

In one preferred embodiment the dispensing container is elasticallydeformable for dispensing a dose of the fluid medicinal product.

To dispense the fluid medicinal product, a force is applied by a meansthat deforms the dispensing container. This force leads to an increasingdeformation of the dispensing container and therefore to an increasingdispensed volume of the fluid medicinal product.

Due to the elastic condition of the dispensing container thisdeformation is reversible. As the force is no longer applied to thedispensing container, it returns to its original shape and size.

In another embodiment the assembly comprises a housing and an actuatorwhich is moveable with respect to the housing.

Inside the housing, a base frame can be located which is moveable withrespect to the housing. The actuator can be located at the distal end ofthat base frame. This actuator can be located between the reservoircontainer and the dispensing container. However, any other suitableposition for the actuator is possible.

The housing forms a good protection for the dispensing container and forthe reservoir container. The reservoir container can be attached to thebase frame.

In one preferred embodiment the actuator is located at the dispensingcontainer for dispensing the fluid medicinal product.

The actuator applies a force to the dispensing container. Due to theapplied force the fluid medicinal product is dispensed. Therefore amechanical contact is needed between the actuator and the dispensingcontainer to apply the force to the dispensing container.

In another preferred embodiment the actuator squeezes the dispensingcontainer and is dispensing the fluid medicinal product.

The actuator applies a force to the dispensing container as it is pushedtowards the dispensing container. The container is deformed and thefluid medicinal product which is contained inside the dispensingcontainer can be dispensed through an outlet.

The force which is applied to the dispensing container can be generatedmechanically or electrically. Therefore, a dispensing means comprising aspring can be located at the distal end of the base frame. Thedispensing means may be connected to the base frame. The actuator can bemoved electrically or by being actuated by the user. The actuator can bemoved back to the starting position by means of the spring.

The dispensing container can dispense a predefined dose of the fluidmedicinal product.

In another preferred embodiment the assembly comprises a dispensingcontainer which is expanding after dispensing the fluid medicinalproduct. Through the expansion a depression is created in the dispensingcontainer which is able to intake fluid medicinal product from thereservoir container.

After the fluid medicinal product is dispensed, a depression is createdinside the dispensing container. As no air can be intaken by the secondoutlet located at the dispensing container by means of a check valve,only fluid medicinal product from the dispensing container can flow intothe dispensing container.

The depression is formed by means of the elastically deformabledispensing container. After being deformed the material tends to returnto its original shape and size. The fluid from the reservoir containerflows into the dispensing container because of the low pressure insidethe dispensing container. During this re-shaping and refilling processthe actuator and therefore the base frame may be pushed back to itsstarting position.

Another advantage of the depression is that the dripping time of aneedle after the injection is reduced.

In another preferred embodiment the assembly comprises additional meansadapted to refill the dispensing container after dispensing the fluidmedicinal product.

The additional means may for example be a pump. The pump is attached torefill the dispensing container.

BRIEF DESCRIPTION OF THE FIGURES

In the following, the invention is described in further detail withreference to the drawings, wherein

FIG. 1 shows a view of the assembly in a starting position.

DETAILED DESCRIPTION

In FIG. 1, identical reference numerals denote identical or comparablecomponents.

FIG. 1 shows an assembly according to the present disclosure. Theassembly is surrounded by a housing 10. The housing 10 comprises a rightside member 12, a left side member 14, a distal bar 16, a first bar 18,a second bar 20 and a proximal bar 22. All of these bars 16, 18, 20, 22comprise a central bore.

A base frame 30 is arranged inside the housing 10 which comprises abearing in which the base frame 30 is movable in axial direction withrespect to the housing 10. The base frame 30 comprises a rightlongitudinal bar 32, a left longitudinal bar 34, a front face 36 of theright longitudinal bar, a front face 38 of the left longitudinal bar, anactuator bar 40, a support bar 42 and a proximal bar 44 of the baseframe.

The actuator bar 40 comprises a bore. A tube 64 is arranged inside thisbore. A check valve is arranged inside the tube 64. The tube 64 isconnecting the reservoir container 70 and the dispensing container 60.

A needle unit 52 is adapted to the distal end 50 of the assembly. Theneedle unit 52 is seated over a second control member 54.

The second control member 54 is located in the flow path between anintermediate member 56 and the needle unit 52. The first bar 18 of thehousing 10 is located between the intermediate member 56 and the outlet58 of the spherical body of the dispensing container 60. The center ofthe first bar 18 comprises a bore to allow for a flow path between thedispensing container 60 and the needle unit 52 passing through the firstbar 18.

At the proximal end 74 of the dispensing container 70, an actuator bar40 is located which comprises a small bore to define an aperture for atube 64 which is connecting the dispensing container 60 with a reservoircontainer 70. On the right and on the left side of the actuator bar 40the front faces 36, 38 of two longitudinal bars are shown. These frontfaces 36, 38 are not flush with the surface of the actuator.

A first control member 66 is arranged at a first outlet 68 located atthe reservoir container 70. The reservoir container 70 is surrounded andconnected to a support bar 42 of the base frame 30 which is comprising acentral opening. This ensures a secure connection of the reservoircontainer 70 to the housing 10.

At the proximal bar 44 of the base frame 44, dose dispensing means 76are shown which comprise a spring 72.

By pressing the dose dispensing means 76, the base frame 30 is pushedtowards the distal end 50 of the housing 10. This movement causes acompression of the dispensing container 60 and liquid medicinal productis dispensed through the needle unit 52.

The distal movement is stopped by the abutment of the front faces 36, 38of the longitudinal bars of the base frame 30 with the first bar 18 ofthe housing 10. The abutment indicates that the maximum dosage of themedicinal product is dispensed. This is the final position of the baseframe during the dispensing process.

Due to the elastic behavior of the dispensing container 60, thedispensing container 60 is withdrawing fluid medicinal product from thereservoir container 70 by suction. This process ends after thedispensing container 60 has reached its original shape.

The check valve 54 ensures that just the fluid medicinal product fromthe reservoir container 70 is flowing into the dispensing container 60by closing the dispensing flow path in proximal direction 74. This is aneffective method to prevent the intaking of air, tissue or blood intothe dispensing container 60.

The spring 72 at the proximal end 74 of the assembly together with theelastic behavior of the dispensing container 60 after dispensing thefluid medicinal product enables the base frame 30 to be pushed back inproximal direction 74. After the dispensing container 60 is refilled,the movement of the base frame 30 ends in its starting position.

The term “drug” or “medicament”, as used herein, means a pharmaceuticalformulation containing at least one pharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a proteine, apolysaccharide, a vaccine, a DNA, a RNA, a antibody, an enzyme, anantibody, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exedin-3 or exedin-4 or an analogue or derivative ofexedin-3 or exedin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N-(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(w-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(w-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2, H-(Lys)5-des Pro36,des Pro37 Exendin-4(1-39)-NH2, des Pro36 [Asp28] Exendin-4(1-39), desPro36 [IsoAsp28] Exendin-4(1-39), des Pro36 [Met(O)14, Asp28]Exendin-4(1-39), des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39), desPro36 [Trp(O2)25, Asp28] Exendin-4(1-39), des Pro36 [Trp(O2)25,IsoAsp28] Exendin-4(1-39), des Pro36 [Met(O)14 Trp(O2)25, Asp28]Exendin-4(1-39), des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28]Exendin-4(1-39); or des Pro36 [Asp28] Exendin-4(1-39), des Pro36[IsoAsp28] Exendin-4(1-39), des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),des Pro36 [Met(O)14, IsoAsp28] Exendin-4(1-39), des Pro36 [Trp(O2)25,Asp28] Exendin-4(1-39), des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39), des Pro36[Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;

or an Exendin-4 derivative of the sequence

H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2, des Asp28 Pro36,Pro37, Pro38Exendin-4(1-39)-NH2, H-(Lys)6-des Pro36, Pro38 [Asp28]Exendin-4(1-39)-NH2, H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28]Exendin-4(1-39)-NH2, des Pro36, Pro37, Pro38 [Asp28]Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28]Exendin-4(1-39)-(Lys)6-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28]Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36 [Trp(O2)25, Asp28]Exendin-4(1-39)-Lys6-NH2, H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25]Exendin-4(1-39)-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25,Asp28] Exendin-4(1-39)-NH2, des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25,Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36[Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2, des Met(O)14 Asp28 Pro36,Pro37, Pro38 Exendin-4(1-39)-NH2, H-(Lys)6-desPro36, Pro37, Pro38[Met(O)14, Asp28] Exendin-4(1-39)-NH2, H-Asn-(Glu)5-des Pro36, Pro37,Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2, des Pro36, Pro37, Pro38[Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-des Pro36, Pro37,Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-Asn-(Glu)5 desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]Exendin-4(1-39)-NH2, H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14,Trp(O2)25, Asp28] Exendin-4(1-39)-NH2, des Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2, H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(S1-39)-(Lys)6-NH2, H-Asn-(Glu)5-des Pro36, Pro37, Pro38[Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2;

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exedin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof. An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

1. An assembly for a drug delivery device comprising a dispensingcontainer and a reservoir container for holding a fluid medicinalproduct, wherein the dispensing container and the reservoir containerare connected to one another and are in fluid communication, and whereinthe dispensing container is squeezable for dispensing a dose of thefluid medicinal product from the dispensing container, the dispensingcontainer being refillable with the fluid medicinal product from thereservoir container.